两性霉素B补料分批发酵工艺优化  

Optimization in Synthesis of Amphotericin B by Fed-Batch Fermentation

作　　者：王昂[1] 王耀耀[1] 仲伟潭[1] 张雪霞[1] 任志红 李敏[1] WANG Ang;WANG Yaoyao;ZHONG Weitan;ZHANG Xuexia;REN Zhihong;LI Min(National Engineering Research Center of Microbial Medicine,Hebei Industry Microbial Metabolic Engineering and Technology Research Center,New Drug Research and Development Company of NCPC,Shijiazhuang 052165,China)

机构地区：[1]微生物药物国家工程研究中心,河北省工业微生物代谢工程技术研究中心,华北制药集团新药研究开发有限责任公司,河北石家庄052165

出　　处：《化学与生物工程》2020年第2期51-54,共4页Chemistry & Bioengineering

摘　　要：为大幅提高产两性霉素B菌株的发酵产抗水平,对外源性短链脂肪酸类前体物质及其添加时机、添加量进行优化,得到了两性霉素B补料分批发酵工艺,即在产两性霉素B菌株发酵培养24~56 h左右,一次性补入2~4 g·L^-1(以发酵液总量计)的丙酸钠。该工艺解决了两性霉素B生物合成途径中内酯环形成的关键性因素,大幅提高了产两性霉素B菌株的发酵产抗水平。经15 t生产罐验证,最终实现了连续3批平均放罐效价达10977μg·mL^-1的发酵产抗水平,与采用原发酵工艺的生产罐批相比,放罐效价提高了39.4%。In order to improve the levels of fermentation and antibiotic-production of Amphotericin B-producing strain,we optimized the exogenous short-chain fatty acids precursor and its adding time and adding amount,and obtained the fed-batch fermentation process of Amphotericin B as follows:adding 2~4 g·L^-1(calculated by the total amount of fermentation liquid)sodium propionate in a once-through operation when the Amphotericin B-producing strain is cultured for 24~56 h.The process solves the key factors of lactone-ring synthesis in the Amphotericin B biosynthetic pathway,and greatly improves the antibiotic-production level of the Amphotericin B-producing strain.The verification in 50 t production tank indicates that the average draw-off titer of three batches is up to 10977μg·mL^-1,which increases by 39.4%compared with that of the original batch.

关 键 词：两性霉素B 前体物质 丙酸钠 补料分批发酵 放罐效价 

分 类 号：R978.1[医药卫生—药品] TQ920[医药卫生—药学]